Effects of long-term active immunization with the second extracellular loop of human β1- or β3-adrenoceptors in thoracic aorta and mesenteric arteries in Lewis rats

Objective To evaluate whether active immunization producing β1- or β3-antibodies (β1-ABs and β3-ABs) detected in sera of patients with dilated cardiomyopathies has deleterious effects on vascular reactivity in Lewis rat thoracic aorta (TA) and small mesenteric arteries (SMA). Design and method Lewis rats were immunized for 6 months with peptidic sequences corresponding to the second extracellular loop of β1- and β3-adrenoceptors (ARs). During the immunization, systolic blood pressure (SBP) was monitored using the tail cuff method. The vascular reactivity of immunized rats was assessed by ex vivo studies on SMA and TA using various β-AR agonists, phenylephrine and KCl. Results The immunizations producing functional β1-ABs and β3-ABs did not affect the SBP. However, in TA from β1-AR-immunized rats, the relaxations mediated by dobutamine and salbutamol were significantly impaired in comparison with adjuvant rats whereas nebivolol-induced relaxation was not modified. Moreover, phenylephrine and KCl-mediated contractions were enhanced in these rats. In contrast, immunization with β3-AR peptide led to the increase of relaxations induced by dobutamine in TA but did not change those induced by salbutamol and nebivolol. Surprisingly, in SMA from both rats immunized with β1- or β3-peptides, relaxations induced by the various β-agonists were not changed whereas phenylephrine and KCl-mediated contractions were impaired. Conclusions Our study shows that β1- and β3-ABs can affect vascular reactivity. β1-ABs would have a pathogenic action whereas β3-ABs would have a beneficial effect on aorta reactivity. Array ( [0] => public://js/js_NhB8QqEMkIRnGegV_fyHSoTNS4QcuYAxmtYDZC610gE.js.gz : fichier présent sur le disque mais absent dans la base de données [1] => public://js/js_YqvqIXMHR_JA_6L7V5VgwgrhCDVtmWC_wCWsaINFQtk.js : fichier présent sur le disque mais absent dans la base de données [2] => public://js/js_YqvqIXMHR_JA_6L7V5VgwgrhCDVtmWC_wCWsaINFQtk.js.gz : fichier présent sur le disque mais absent dans la base de données [3] => public://js/js_NhB8QqEMkIRnGegV_fyHSoTNS4QcuYAxmtYDZC610gE.js : fichier présent sur le disque mais absent dans la base de données

HPV vaccine: an overview of immune response, clinical protection, and new approaches for the future

Although long-term protection is a key-point in evaluating HPV-vaccine over time, there is currently inadequate information on the duration of HPV vaccine-induced immunity and on the mechanisms related to the activation of immune-memory. Longer-term surveillance in a vaccinated population is needed to identify waning immunity, evaluating any requirements for booster immunizations to assess vaccine efficacy against HPV-diseases. Current prophylactic vaccines have the primary end-points to protect against HPV-16 and 18, the genotypes more associated to cervical cancer worldwide. Nevertheless, data from many countries demonstrate the presence, at significant levels, of HPVs that are not included in the currently available vaccine preparations, indicating that these vaccines could be less effective in a particular area of the world. The development of vaccines covering a larger number of HPVs presents the most complex challenge for the future. Therefore, long term immunization and cross-protection of HPV vaccines will be discussed in light of new approaches for the future

Pratiques funéraires néolithiques en Eure-et-Loir (28), exemple d'un petit dolmen beauceron

Résumé de la 1833e réunion scientifique de la société d'Anthroplogie de Paris "Autour de la Méditerranée, de la préhistoire à nos jours. - Hommes et peuplements/interactions bioculturelles - Marseille 23-25 Janvier 2008 dans Bulletins et Mémoires de la Société d'Anthropologie de Paris, n.s. , t.19 , 3-4, 265-29

Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV) L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8) or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2) vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type.Multivalent vaccination via in vivo electroporation requires spatial separation of individual type L1 DNA vaccines

Protection of Rabbits against Challenge with Rabbit Papillomaviruses by Immunization with the N Terminus of Human Papillomavirus Type 16 Minor Capsid Antigen L2▿

Current L1 virus-like particle (VLP) vaccines provide type-restricted protection against a small subset of the human papillomavirus (HPV) genotypes associated with cervical cancer, necessitating continued cytologic screening of vaccinees. Cervical cancer is most problematic in countries that lack the resources for screening or highly multivalent HPV VLP vaccines, suggesting the need for a low-cost, broadly protective vaccinogen. Here, N-terminal L2 polypeptides comprising residues 1 to 88 or 11 to 200 derived from HPV16, bovine papillomavirus type 1 (BPV1), or cottontail rabbit papillomavirus (CRPV) were produced in bacteria. Rabbits were immunized with these N-terminal L2 polypeptides and concurrently challenged with CRPV and rabbit oral papillomavirus (ROPV). Vaccination with either N-terminal L2 polypeptides of CRPV effectively protected rabbits from CRPV challenge but not from papillomas induced by cutaneous challenge with CRPV genomic DNA. Furthermore, papillomas induced by CRPV genomic DNA deficient for L2 expression grew at the same rate as those induced by wild-type CRPV genomic DNA, further suggesting that the L2 polypeptide vaccines lack therapeutic activity. Neutralizing serum antibody titers of >15 correlated with protection (P < 0.001), a finding consistent with neutralizing antibody-mediated protection. Surprisingly, a remarkable degree of protection against heterologous papillomavirus types was observed after vaccination with N-terminal L2 polypeptides. Notably, vaccination with HPV16 L2 11-200 protected against cutaneous and mucosal challenge with CRPV and ROPV, respectively, papillomaviruses that are evolutionarily divergent from HPV16. Further, vaccination with HPV16 L2 11-200 generates broadly cross-neutralizing serum antibody, suggesting the potential of L2 as a second-generation preventive HPV vaccine antigen

Air-conditioning and the adaptation cooling deficit in emerging economies

Increasing temperatures will make space cooling a necessity for maintain comfort and protecting human health, and rising income levels will allow more people to purchase and run air conditioners. Here we show that, in Brazil, India, Indonesia, and Mexico income and humidity-adjusted temperature are common determinants for adopting air-conditioning, but their relative contribution varies in relation to household characteristics. Adoption rates are higher among households living in higher quality dwellings in urban areas, and among those with higher levels of education. Air-conditioning is unevenly distributed across income levels, making evident the existence of a disparity in access to cooling devices. Although the adoption of air-conditioning could increase between twofold and sixteen-fold by 2040, from 64 to 100 million families with access to electricity will not be able to adequately satisfy their demand for thermal comfort. The need to sustain electricity expenditure in response to higher temperatures can also create unequal opportunities to adapt

Durable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17–36 epitopes

Vaccination with the minor capsid protein L2, notably the 17–36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17–36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]. Mice were vaccinated three times subcutaneously with AAVLP (HPV16/31L2) at two week intervals at several doses either alone or formulated with alum, alum and MPL, RIBI adjuvant or Cervarix. The use of adjuvant with AAVLP (HPV16/31L2) was necessary in mice for the induction of L2-specific neutralizing antibody and protection against vaginal challenge with HPV16. While use of alum was sufficient to elicit durable protection (>3 months after the final immunization), antibody titers were increased by addition of MPL and RIBI adjuvants. To determine the breadth of immunity, rabbits were immunized three times with AAVLP (HPV16/31L2) either alone, formulated with alum±MPL, or RIBI adjuvants, and after serum collection, the animals were concurrently challenged with HPV16/31/35/39/45/58/59 quasivirions or cottontail rabbit papillomavirus (CRPV) at 6 or 12 months post-immunization. Strong protection against all HPV types was observed at both 6 and 12 months post-immunization, including robust protection in rabbits receiving the vaccine without adjuvant. In summary, vaccination with AAVLP presenting HPV L2 17–36 epitopes at two sites on their surface induced cross-neutralizing serum antibody, immunity against HPV16 in the genital tract, and long-term protection against skin challenge with the 7 most common oncogenic HPV types when using a clinically relevant adjuvant.Medigene AG to NDC and RBSR, and Public Health Service (grants.nih.gov) grants P50 CA098252 and CA118790 to RBSR

Neutralizing antibody titer and antibody response of sera from mice vaccinated with L1 or L2×8 delivered as protein or a DNA vaccine via electroporation.

<p>Balb/c mice were vaccinated three times at two week intervals with PBS, 10 µg L2×8 DNA vaccine i.m. with electroporation three times, or twice utilizing 10 µg HPV16 L1 DNA vaccine i.m. with electroporation followed by a single boost with 25 ug L2×8 protein in alum s.c., 10 µg HPV16 L1 DNA vaccine i.m. with electroporation three times, three times with 10 µg L2×8 DNA vaccine i.m., or 25 ug L2×8 protein in alum s.c., or Gardasil s.c.,,. Serum samples were collected two weeks after the third vaccination, and were tested for in vitro HPV16 neutralization titer (A) and antibody response to HPV16 L2 (B) as measured by ELISA. (C) To assess relative levels of expression, 293TT cells were transfected with no plasmid, HPV16 L1+L2 DNA in pShell, full length HPV16 L2 DNA in p16L2h, bacterial codon optimized L2×8 DNA in pcDNA, or human codon optimized L2×8 in pcDNA. 293TT cells were lysed two days after transfection. Western blotting was performed with lysate samples using a monoclonal antibody to HPV16 L2 17–36.</p

A comparison of antibody responses of mice vaccinated with DNA expressing L1 or L1+L2 of HPV6, 16, or 18, either singly or together at the same or different sites.

<p>Balb/c mice were vaccinated i.m. with electroporation three times at two week intervals with 20 µg each of DNA expressing L1 or L1+L2 of HPV6, HPV16, and HPV18, either individually, or together at the same site or each at a different site (DS), or s.c. with Gardasil. Serum samples were harvested at two weeks after the third vaccination (A–C) or 3 months after the third vaccination (D–F), and neutralizing antibody titers were measured with HPV6 (A,D), HPV16 (B,E), or HPV18 PsV (C,F). Antibody response to L2 was measured by ELISA against full length HPV16 L2 with serum samples collected two weeks after the third vaccination (G).</p